Gene Signature of the Human Pancreatic ε Cell

Gutiérrez, Giselle Domínguez; Kim, Jinrang; Lee, Ann–Hwee; Tong, Jenny; Niu, Jingjing; Gray, Sarah M.; Wei, Yi; Ding, Yueming; Ni, Min; Adler, Christina; Murphy, Andrew; Gromada, Jesper; Xin, Yurong

doi:10.1210/en.2018-00833

Cited by 23 publications

(10 citation statements)

References 77 publications

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“…Spatial transcriptomics may also provide more reliable avenues for scRNA-Seq, as they avoid confounders associated with islet dissociation and would allow the field an unbiased perspective to determine whether heterogeneity of gene expression is spatially driven ( 82 ), as was recently suggested ( 35 , 83 ). Newer 3′-based methods that allow for higher throughput, and greater sample sizes at reasonable cost, have allowed the identification of rarer populations, such as ε-cells ( 84 ). Targeted sequencing approaches, such as droplet-assisted RNA targeting by single-cell sequencing (DART-Seq), significantly improve coverage by targeting the limited depth of scRNA-Seq to a subset of preselected transcripts of interest ( 85 ).…”

Section: Future Outlookmentioning

confidence: 99%

Navigating the Depths and Avoiding the Shallows of Pancreatic Islet Cell Transcriptomes

Mawla

Huising

2019

Diabetes

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Islet gene expression has been widely studied to better understand the transcriptional features that define a healthy β-cell. Transcriptomes of FACS-purified α-, β-, and δ-cells using bulk RNA-sequencing have facilitated our understanding of the complex network of cross talk between islet cells and its effects on β-cell function. However, these approaches were by design not intended to resolve heterogeneity between individual cells. Several recent studies used single-cell RNA sequencing (scRNA-Seq) to report considerable heterogeneity within mouse and human β-cells. In this Perspective, we assess how this newfound ability to assess gene expression at single-cell resolution has enhanced our understanding of β-cell heterogeneity. We conduct a comprehensive assessment of several single human β-cell transcriptome data sets and ask if the heterogeneity reported by these studies showed overlap and concurred with previously known examples of β-cell heterogeneity. We also illustrate the impact of the inevitable limitations of working at or below the limit of detection of gene expression at single cell resolution and their consequences for the quality of single–islet cell transcriptome data. Finally, we offer some guidance on when to opt for scRNA-Seq and when bulk sequencing approaches may be better suited.

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Section: Future Outlookmentioning

confidence: 99%

Navigating the Depths and Avoiding the Shallows of Pancreatic Islet Cell Transcriptomes

Mawla

Huising

2019

Diabetes

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“…The Hill and Sussel group suggested that the upregulation of ghrelin under Nkx2.2 null conditions is not due to the loss of the ghrelin promoter and considered that Nkx2.2 contributes to the activation of ghrelin in mature ε cells [47]. This was supported by Dominguez Gutierrez et al using single human islet cell RNA sequencing [49]. Regarding Pax6, which is a key factor for generating neural neuronal lineages in the central nervous system and differentiating non-neuronal lineages of the eye [50,51], Swisa and colleague revealed that the absence of Pax6 inhibited production of β cells and induced increase of ε cells using db/db mice, a Type 2 DM animal model (Figure 1A) [52].…”

Section: ε Cell Developmentmentioning

confidence: 99%

Development and Characteristics of Pancreatic Epsilon Cells

Sakata

Yoshimatsu

Kodama

2019

IJMS

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Pancreatic endocrine cells expressing the ghrelin gene and producing the ghrelin hormone were first identified in 2002. These cells, named ε cells, were recognized as the fifth type of endocrine cells. Differentiation of ε cells is induced by various transcription factors, including Nk2 homeobox 2, paired box proteins Pax-4 and Pax6, and the aristaless-related homeobox. Ghrelin is generally considered to be a “hunger hormone” that stimulates the appetite and is produced mainly by the stomach. Although the population of ε cells is small in adults, they play important roles in regulating other endocrine cells, especially β cells, by releasing ghrelin. However, the roles of ghrelin in β cells are complex. Ghrelin contributes to increased blood glucose levels by suppressing insulin release from β cells and is also involved in the growth and proliferation of β cells and the prevention of β cell apoptosis. Despite increasing evidence and clarification of the mechanisms of ε cells over the last 20 years, many questions remain to be answered. In this review, we present the current evidence for the participation of ε cells in differentiation and clarify their characteristics by focusing on the roles of ghrelin.

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“…Many studies have described the scRNA-seq profiles of human islets and identified the constituent cell types and their corresponding transcriptional signatures, including the less abundant δ, ε and PP cells (Baron et al, 2016;Li et al, 2016;Muraro et al, 2016;Segerstolpe et al, 2016;Wang et al, 2016b;Xin et al, 2016a;Lawlor et al, 2017;Dominguez Gutierrez et al, 2018). These datasets validated the previously known features of each cell type but have also discovered novel signatures that may play roles in cell identity and function (Box 2).…”

Section: Conversion Of Endocrine Cellsmentioning

confidence: 91%

“…• δ Cells express several vital receptor genes, such as LEPR and GHSR, which bind leptin and ghrelin, respectively, indicating the role of δ cells in integrating paracrine and metabolic signals (Baron et al, 2016;Muraro et al, 2016;Segerstolpe et al, 2016;Lawlor et al, 2017). • Compared with other endocrine cell types, ε cells express a specific group of genes, including cell-surface receptors for neuropeptides, metabolites, hormones and others (Segerstolpe et al, 2016;Dominguez Gutierrez et al, 2018). • PP cells display a gene expression profile that resembles neuronal cells, which supports previous observations (van Arensbergen et al, 2010) and suggests either similarity in cell function or developmental proximity (Muraro et al, 2016).…”

Section: Exogenous Production Of β Cells From Hescsmentioning

confidence: 99%

Understanding generation and regeneration of pancreatic β cells from a single-cell perspective

2020

Development

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Understanding the mechanisms that underlie the generation and regeneration of β cells is crucial for developing treatments for diabetes. However, traditional research methods, which are based on populations of cells, have limitations for defining the precise processes of β-cell differentiation and trans-differentiation, and the associated regulatory mechanisms. The recent development of single-cell technologies has enabled re-examination of these processes at a single-cell resolution to uncover intermediate cell states, cellular heterogeneity and molecular trajectories of cell fate specification. Here, we review recent advances in understanding βcell generation and regeneration, in vivo and in vitro, from single-cell technologies, which could provide insights for optimization of diabetes therapy strategies.

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Gene Signature of the Human Pancreatic ε Cell

Cited by 23 publications

References 77 publications

Navigating the Depths and Avoiding the Shallows of Pancreatic Islet Cell Transcriptomes

Navigating the Depths and Avoiding the Shallows of Pancreatic Islet Cell Transcriptomes

Development and Characteristics of Pancreatic Epsilon Cells

Understanding generation and regeneration of pancreatic β cells from a single-cell perspective

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